Association between essential hypertension and polymorphisms of beta 1 adrenergic receptor gene G1165C (Gly389Arg) in Chinese Mongolian population

BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between the polymorphism of beta1 adrenergic receptor （β1-AR） gene G1165C （Arg389Gly）, an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN ： A cross-sectional study SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure： ① Normal blood pressure group （n=117）： systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg =0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group （n=122）： including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS ： The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood （5 mL） was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C （Gly389Arg） genotype were detected with the Sequenom system. Polymerase chain reaction （PCR） experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CO were calculated. MAIN OUTCOME MEASURES： The distributions of β1-AR Gl165C （Gly389Arg） genotypes and alleles were observed. RESULTS： A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C （Gly389Arg） genotypes and allele distnbutions： In Mongolian population, the frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site in the essential hypertension group （72%, 28%） were not significantly different from those in the normal blood pressure group （67%, 33%） （xz=0.841, P=-0.359; OR 0.773, 95%Cl： 0.445-1.342）; The frequencies of C and G alleles also had no significant differences between the essential hypertension group （85%, 15%） and the normal blood pressure group （82%, 18%） （x^2=1.136, P=-0.287; OR： 0.769, 95%Cl： 0.747-1.248）. ②The frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site had no significant differences between the patients with simple high SBP （71%, 29%） and the normal blood pressure group （x^2=0.250, P=-0.617; OR： 0.833, 95%C/： 0.408-1.703）; The frequencies of C and G alleles were not significantly different between the patients with simple high SBP （86%, 14%） and the normal blood pressure group （x^2=0.670, P=-0.413; OR 0.766, 95%Cl： 0.404-1.453）. CONCLUSION： In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C （Gly389Arg） have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension （including simple SBP increase）, which suggests that G1165C （Glu389Asp） site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.

Role of β-Adrenergic Signal Transduction Pathway on Myocardial Ischemic Preconditioning of Rats

To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1＋, 2＋, 3＋ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group （P〈0. 001）, while the enzymes were significantly higher in I/R （P〈0. 001）. The Bmax of β-AR in IP was much higher than that in I/R （P〈0. 001）, but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R （P〈0.05, 0. 002 and 0. 001, respectively）. In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .

Jueming Prescription(决明方) Reduces Body Weight by Increasing the mRNA Expressions of Beta3-Adrenergic Receptor and Uncoupling Protein-2 in Adipose Tissue of Diet-Induced Obese Rats

Objective： To investigate the antiobesity effect of Jueming Prescription （决明方, JMP）, a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor （beta3-AR） and uncoupling protein-2 （UCP-2） in adipose tissue of diet-induced obese rats. Methods： Fifty male Sprague-Dawley rats were randomly divided into the normal control group （n=8） that was on a standard chow diet, and the obese model group （n=42） that was on a diet of high fat chow. Two weeks after the high fat diet, 29 obese rats in the obese model group were further randomly divided into 3 groups： the untreated obese model group （n=9）, the met＇formin group （n=10, mefformin 300 mg-kg-1.day-1）, and the JMP group （n=10, JMP 4 g.kg-1.dayl）. After 8-week treatment, body weight, wet weight of visceral fat, and percentage of body fat （PBF） were measured. The levels of fasting blood glucose, serum lipids, and insulin were assessed, and insulin sensitivity index （ISI） was calculated. The adipose tissue section was stained with hematoxylin-Eosin, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the pet-renal fat tissue were determined by real-time reverse transcription polymerase chain reaction （RT-PCR）. Results： Compared with the obese model group, treatment with JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF, and diameter of adipocytes, and significantly higher level of high-density lipoprotein cholesterol, ISI （all P〈0.01）, JMP increased the mRNA expressions of beta3-AR and UCP-2 from pedrenal fat tissue （P〈0.05, P〈0.01）. Conclusions： JMP could reduce body weight and adipocyte size; and the effect was associated with the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and improvement of insulin sensitivity.

肾上腺素、去甲肾上腺素刺激培养的大鼠心肌细胞凋亡

目的 :观察肾上腺素 ( AD)或去甲肾上腺素 ( NA)刺激体外培养的大鼠心肌细胞凋亡 ,探讨其作用机制。方法 :大鼠心肌细胞分别暴露于 10 - 7mol/L 的 NA,10 - 7m ol/L 的 AD,NA+酚妥拉明 ( 10 - 7m ol/L) ,NA+艾司洛尔 ( 10 - 7mol/L) ,AD+酚妥拉明 ( 10 - 7m ol/L)或 AD+艾司洛尔 ( 10 - 7mol/L) 2 4 h。流式细胞仪检测凋亡水平。结果 :NA使凋亡细胞百分率由 ( 4 .2± 1.6) %增加到 ( 10 .0± 5 .0 ) % ( P<0 .0 1;n=8) ,此作用可被艾司洛尔完全抑制 ,而不受酚妥拉明影响。AD与 NA的作用相仿 ,使凋亡细胞百分率增加到 ( 12 .8± 7.9) % ,且 AD诱导的凋亡同样被艾司洛尔完全抑制但不受酚妥拉明的影响。结论 :AD和 NA可能通过激活 β肾上腺素能通路 。

Effects of hexametazidine on physiological properties of guinea-pig papillary muscles

Effects of hexametazidine [1,4-di(2,3,4-trimethoxybenzyl)piperazine] on the physiological properties of guinea-pig papillary muscles were investigated. Hexametazidine possesses a concentration-dependent negative inotropic effect (IC_(50)=81.8±16.9μmol/L).The effect of hexametazidine(30.8μmol/L)was antago- nized completely by increasing the concentration of Ca^(2+)from 1.8 to 5.4mmol/L. Hexametazidine(30.8μmol/L)increased the threshold concentration of adrenaline for inducing the automaticity of the muscles from 3.95±1.80 to 6.67±4.84μmol/L (P<0.05).It prolonged the functional refractory period from 218±14 to 254±20ms (P<0.05)at the concentration of 61.6μmol/L.Hexametazidine(6.2μmol/L)antago- nized the positive inotropic effect of isoprenaline competitively and of histamine non-competitively(pA 2 and pD2′ values were 5.45 and 4.13, respectively).

肾上腺素β受体和胆碱能M受体对边缘细胞钾离子转运的调控

耳蜗血管纹边缘细胞向内淋巴转运钾离子对耳蜗内淋巴的生成,电化学特征的维持起到直接作用。钾离子经边缘细胞转运的过程除了受细胞内外离子浓度、膜电压的调控外还受细胞膜受体及细胞内信号转导系统调节。目前研究发现肾上腺素β受体促进边缘细胞的钾离子转运;胆碱能M受体则抑制边缘细胞的钾离子转运。肾上腺素β受体和胆碱能M受体对边缘细胞钾离子转运的调控作用具有重要的临床意义。